Exploring the effects and mechanism of action of HXP on H22hepatocellular tumor-bearingmice tumorigenesis based on PI3K/AKT/mTOR signaling pathway
Purpose:To investigate the effect of Heshu Xiaoji prescription(HXP)on tumorigenesis in H22hepatocellular tumor-bearing mice as well as on PI3K/AKT/mTOR signaling pathway-related proteins through in vivo experiments and to ex-plore the inhibitory tumor growth mechanism of action.Methods:H22hepatocellular tumor-bearing mice model was prepared,and the mice were randomly divided into blank control group,model group,HXP low,medium and high dose groups(1.37,2.73,5.46g/kg),sorafenib group(0.03g/kg),and combined group(5.46g/kg of HXP combined with 0.03g/kg of sorafenib).From the 6thday of inoculation,the mice were administered for 14consecutive days.The mice were weighed and the general conditions were observed.On the next day of the last administration,the mice were sacrificed,and the tumor was removed and weighed to calculate the anti-tumor rate.Hematoxylin-eosin(HE)staining was used to observe the morphological changes of the tumor tis-sues,enzyme-linked immunosorbent assay(ELISA)was used to detect the content of IL-1β and TNF-α in the homogenate of the tumor tissues,and immunohistochemistry and Western-blotting were used to detect the expression of proteins related to the PI3K/Akt/mTOR pathway.Results:HXP significantly improved the mental and activity status of H22hepatocellular tumor-bear-ing mice.The tumor inhibition rates of HXP low,medium and high dose groups,sorafenib group,and the combination group were 23.9%,38.6%,64.5%,53.1%,and 76.6%,respectively(P<0.05);compared with the model group,the therapeutic groups could significantly reduce the density of the tumor cells,cause tumor Compared with the model group,the content of IL-1β in the tumor tissues of each administration group was elevated to different degrees(P<0.05),and the content of TNF-α in HXP high-dose group,the sorafenib group,and the combination group was elevated to different degrees(P<0.05).PI3K,Akt,mTOR protein expression were significantly decreased in the combined group and the HXP high-dose group;Western-blotting results suggested that P-PI3K,P-Akt,P-mTOR protein expression was significantly decreased in the treatment groups compared with the model group,and the protein expression of P-PI3K/PI3K,P-Akt/Akt,P-mTOR/mTOR were significantly decreased in HXP medium and high dose groups,sorafenib group,and the combined group(P<0.05).Conclusion:HXP has significant in-hibitory effect on H22hepatocellular tumor-bearing mice,and its mechanism of action may be related to the inhibition of key pro-tein expression in the PI3K/AKT/mTOR signaling pathway.